N. V. Ryazantseva

Role of NF-kB, p53, and p21 in the Regulation of TNF-α Mediated Apoptosis of Lymphocytes

The effect of recombinant TNF-α on programmed death of donor lymphocytes was studied in vitro. The proapoptotic effect of this cytokine is realized through transcription factors and cell cycle inhibitors. Incubation of lymphocytes with recombinant TNF-α revealed increased levels of NF-kB and p21 and reducted content of nonphosphorylated p53.

Role of genetically determined production of immunoregulatory cytokines in immunopathogenesis of chronic viral hepatitides.

Immunopathogenesis of chronic viral hepatitides was studied by modern immunological, molecular, genetic methods. We revealed an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes (primarily of the Th2 type). The risk of progression and chronic course of viral hepatitides in Caucasian population was associated with alleles of promoter regions −330G and −592A in the IL-2 and IL-10 genes, respectively, as well as with the T/T genotype of the polymorphic region C590T in the IL-4 gene. The C/C genotype of the IL-10 gene promoter region C592A was shown to be a factor determining resistance to long-term persistence of hepatitis B and C viruses.

Chronic tick-borne encephalitis virus antigenemia: possible pathogenesis pathways.

Study of the proliferative potential and immunophenotype of lymphocytes and cytokine-producing capacity of mononuclear cells in patients with chronic tick-borne encephalitis virus antigenemia showed changes in T cell lymphoproliferative response, relative content of T cells and T helper inductors, immunoregulatory index, and imbalance in the production of immunoregulatory Th1 and Th2 cytokines.

Effects of HSP27 Chaperone on THP-1 Tumor Cell Apoptosis

The role of Hsp27 (heat shock protein 27) chaperone in regulation of THP-1 tumor cell apoptosis was studied. Realization of tumor cell apoptosis under conditions of in vitro culturing with Hsp27 specifi c inhibitor (KRIBB3) was evaluated by fluorescent microscopy with FITC-labeled annexin V and propidium iodide. Measurements of Bcl-2 family proteins (Bcl-2, Bax, Bad) in tumor cells incubated with Hsp27 inhibitor were carried out by Western blotting. Chaperone Hsp27 acted as apoptosis inhibitor in THP-1 tumor cells modulating the proportion of antiapoptotic (Bcl-2) and proapoptotic (Bax and Bad) proteins.

Role of recombinant mitogen-activated protein kinases JNK and p38 in the regulation of apoptosis in blood mononuclear cells under conditions of oxidative stress in vitro

Programmed death of peripheral blood mononuclear cells from healthy donors was studied during culturing with various concentrations of H2O2 and selective inhibitors of JNK (SP600125) and p38 MAPK (ML3403). In vitro incubation of mononuclear leukocytes with 1 mM H2O2 stimulated apoptotic cell death. Treatment with inhibitors (SP600125 and ML3403) during in vitro oxidative stress prevented the increase in the number of annexin-positive mononuclear cells. Our results indicate that MAP kinases JNK and p38 are involved in the mechanisms of oxidative dysregulation of apoptosis.

Changes in the lipid phase of erythrocyte membranes in patients with paranoid schizophrenia.

Considerable changes in the lipid phase of erythrocyte membranes were found in patients with paranoid schizophrenia. During exacerbation and remission of the disease the content of phosphatidylethanolamine decreases, while the amount of lysophosphatidylcholine decreases. These changes are accompanied by an increase in erythrocyte membrane microviscosity. Structural modification of the lipid phase in erythrocyte membranes in patients with schizophrenia is associated with intensification of lipid peroxidation.

Typical Changes of Erythrocytes in Chronic Inflammation

Structural and metabolic status and function of erythrocytes were studied in patients with chronic bronchitis, chronic inflammatory diseases of the upper airways, and chronic colitis. Complex study of the peripheral component of the erythron showed that disorders in erythrocyte morphology and function (decreased erythrocyte dry weight, low concentration of sulfhydryl groups and lipoproteins, decreased content of high molecular weight polypeptides in parallel with increased content of low molecular weight proteins, increased number of transformed cells, and enhanced reversible aggregation) were nonspecific and did not depend on the location of the inflammatory process.

Structure and Properties of Lipid Bilayer of Erythrocyte Membranes in Patients with Malignant Tumors

The study of erythrocyte membranes in untreated patients with malignant tumors of different location (lung cancer, tumors of the head and neck, stomach and colorectal cancer) revealed changes in the fatty-acid spectrum of phospholipid fraction paralleled by an increase in the viscosity of the lipid bilayer, including the area of protein-lipid contacts. The degree of changes depended on tumor location.

Effect of Galectin-1 on Apoptosis of CD4+ Lymphocytes Differentiated In Vitro Towards Regulatory T Cells

We studied the effect of galectin-1 on apoptosis of CD4+ lymphocytes intact and in vitro differentiated towards regulatory T cells. An increase in the content of apoptotic CD4+ lymphocytes was observed after exposure of intact cells with 15 ng/ml galectin-1 and after exposure of regulatory T cells with 10 and 15 ng/ml galectin-1. Apoptosis of regulatory T cells induced by galectin-1 was accompanied by an increase in the content of proapoptotic protein Bad.

Cytokine mediated apoptosis of granulocyte eosinophils in expressed blood eosiniphilia

Programmed cell death induced by recombinant cytokines (IL-5, IL-3 and eotaxin) of eosinophils isolated from patients with expressed blood eosinophilia (malignant diseases of the blood system, opisthorchosis) has been examined. It was demonstrated that an initially low level of spontaneous apoptosis is registered in all surveyed patients. r-IL-5, r-IL-3 and r-eotaxin treatment of eosinophils isolated from the peripheral blood of opisthorchosis patients and cultivated in vitro suppressed apoptosis. However, eosinophils isolated from patients with malignant diseases associated with expressed blood eosinophilia were insensitive to the cytokines.